Cancer is the second leading cause of death in the United States. Half of all men and one-third of all women in the U.S. will develop cancer during their lifetimes.
Cancer is a condition which develops when abnormal cells in an organ begin to grow uncontrollably, replacing normal tissue. This cell proliferation usually forms tumors, although it may also be blood borne. Cancers may behave differently. For instance, breast cancer may grow at a different rate than lung cancer. Although treatment is usually directed to the different characteristics of the particular cancer, most cancer treatment involves chemotherapeutic agents.
Breast cancer is the second leading cause of cancer deaths among women in the United States. Second only to lung cancer, breast cancer is the leading cause of cancer deaths among women aged 40 to 55 years. Breast cancer is the most common malignant neoplasm in women worldwide. The American Cancer Society estimated that in 2001, about 192,200 new cases of invasive breast cancer would be diagnosed among women in the United States. In addition, an estimated 1500 cases would be diagnosed among men. Statistics indicate that in 2001, there were about 40,200 deaths from breast cancer in the United States.
The development of breast cancer has long been speculated to be linked to estrogen stimulation derived from the ovaries. In 1900, Stanley Boyd demonstrated that one-third of the premenopausal women diagnosed with breast cancer benefited from ovarectomies (removal of ovaries). It is now known that the reduction of the estrogen levels that accompany ovarectomy is responsible for this effect, and that any form of endocrine therapy that decreases estrogen levels will benefit approximately one-third of breast cancer patients with pre- or post-menopausal breast cancer.
One of the risk factors associated with increased chance of breast cancer development is genetic predisposition. A woman with a first-degree relative with breast cancer is about two to three times more likely to develop breast cancer than a woman with a negative family history. Most of the patients with hereditary breast cancer are thought to have a mutant BRACA1 or BRACA2 gene. In one study of 33 families with evidence of linkage to BRACA1 or BRACA2 gene, the lifetime risk of breast cancer was 87% by age 70.
Breast cancer treatments include surgery, radiation, and chemothereapy. Chemotherapeutic agents and regimens with documented antitumor activity against breast cancer, however, have limited success in treating the disease, as less than one in five patients with stage IV breast cancer are alive five years from the first detection of distant metastases. Although improved response has been observed, overall survival for patients with metastatic breast cancer has not been significantly improved by the progress of the past three decades. Furthermore, despite the proven benefit of adjuvant systemic therapy in reducing the risk of recurrence, a significant fraction of patients with early stage breast cancer still will relapse and ultimately die of metastatic disease. Clearly new active agents and strategies are needed to improve upon this situation.
It is therefore an object of the present invention to provide novel 1-adamantyl compounds for the treatment of breast cancer and other proliferative disorders.
It is a further object of the present invention to provide novel pharmaceutical compositions of 1-adamantyl compounds for the treatment of breast cancer and other proliferative disorders.
It is still another object of the present invention to provide a method for treating tumors from breast cancer and other proliferative disorders by administering to a subject in need of such treatment a therapeutically effective amount of novel 1-adamantyl compounds.
It is yet another object of the present invention to provide a method for treating tumors from breast cancer and other proliferative disorders by administering to a subject in need of such treatment a therapeutically effective amount of novel 1-adamantyl compounds in combination with other anti-tumor agents.